Cancer Risk Triples in Kids with Arthritis

Action Points

Children with juvenile idiopathic arthritis (JIA) have a nearly threefold increased risk for malignancy, even if they were never treated with biologic therapies.

Point out that patients, ages 12 to 17, were at decreased risk of malignancy compared to patients 18 and older.

Children with juvenile idiopathic arthritis (JIA) had a nearly threefold increased risk for malignancy, even if they had never been treated with biologic therapies, researchers found.

The overall incidence rate of cancer among children with JIA who had received only conventional therapy was 67 cases per 100,000 person-years (95% CI 1.3 to 132.5), while the rate among healthy children was 23.2 cases per 100,000 person-years (95% CI 12.2 to 34.2), according to Beth Nordstrom, PhD, of United BioSource Corporation in Lexington, Mass., and colleagues.

Accordingly, the hazard ratio for cancer among biologic-naive children was 2.81 (95% CI 0.94 to 8.34), the researchers reported in the September Arthritis Care & Research.

Adults with rheumatoid arthritis are at increased risk for certain cancers, particularly lymphoma, which is thought to relate to the underlying immune system dysregulation and high levels of systemic inflammation.

In addition, treatment with tumor necrosis factor (TNF) inhibitors may contribute to the risk, because of the role TNF itself plays in tumor surveillance.

Since children with JIA began receiving treatment with the biologic agents, questions have arisen regarding cancer risks, adding to uncertainty as to whether the disease itself in younger patients also is associated with malignancy.

In an attempt to sort through the possible risks of the disease and its treatment in young patients, Nordstrom and colleagues conducted a case-control study that included 3,605 patients diagnosed with JIA before age 16 and 37,689 controls from a large administrative database.

Mean age was 11, and the majority were female.

During 5,974 person-years of follow-up, malignancies other than nonmelanoma skin cancer and carcinoma in situ were diagnosed in 0.1% of the JIA group.

In contrast, during 73,395 person-years of follow-up, 0.05% of controls were diagnosed with cancer.

The standardized incidence rates for both case and control groups were higher than the standardized incidence rates in the Surveillance, Epidemiology, and End Results (SEER) database, though only among cases was the rate significantly higher (SIR 4.03, 95% CI 2.56 to 5.99).

Patients ages 12 to 17 were at decreased risk compared to patients age 18 and over (HR 0.18, 95% CI 0.05 to 0.68).

The total numbers of probable or highly probable cancers were small, with four among JIA cases and 17 among controls, so separate analyses could not be done for most individual types of malignancies.

However, the SIR for lymphoma was significantly higher at 14.81 (95% CI 7.62 to 25.67) in the JIA group, "suggesting that lymphoma may be among the primary drivers of any risk of cancer in JIA," the researchers observed.

Two of the JIA patients had been treated with methotrexate, and calculation of their risk separately found an HR of 5.47 (95% CI 1.26 to 23.70, P<0.05), which was significantly higher than for all JIA combined.

A possible explanation for this finding was that methotrexate was likely to have been given to children with more severe disease, although an earlier study examining cancer rates before methotrexate became available in the 1980s did not rule out the possibility that there may be a methotrexate-related increase in risk.

Nordstrom and colleagues acknowledged that their study was not designed to assess risks associated with methotrexate, but rather those from treatment with biologics, which generally are only used when methotrexate fails.

"Therefore, it is reasonable to assess the cancer risk in methotrexate-treated JIA patients as a baseline for understanding any excess risk conferred by an anti-TNF agent," they argued.

Limitations of the study include its reliance on administrative claims data, a lack of information on race, and probable closer monitoring of children with JIA that could detect cancers more quickly.

And despite the large study population, the small numbers of JIA patients and malignancies overall do not permit definitive assumptions from being drawn about safety of TNF inhibitors in children.

"We propose that the interpretation of the risk of cancer in JIA patients treated with biologic agents should be made with consideration for the potential increased risk associated with JIA and conventional treatment," Nordstrom and colleagues stated.

Several co-authors are employees of Pfizer. One co-author owns stock in Vanguard Healthcare, while another has stock in Pfizer, and a third holds stock in Wyeth.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner